DESCRIPTION: (Adapted from applicant's description) The timing of and mechanism by which early exposure to uncontrolled diabetes causes abnormalities during preimplantation phase remain to be discovered. The study proposed will attempt to show that the maternal diabetic state initiates a dely in development between ovulation and the 1-cell stage immediately following fertilization. To prove this hypothesis, embryos will be removed at three different stages (a) metaphase II-arrested ooctes, (b) 1-cell embryo, or (c) 2-cell embryo. Oocytes are fertilized in vitro and all embryos are transferred into either diabetic or non-diabetic mice. All embryos will be recovered 48-72 hours later and developmental stages reached by the embryos will be examined. The second portion of this study will attempt to explore the hypothesis that glutathione (GSH) depletion due to oxidative stress is related to the developmental delay. To test this hypothesis, glutathione levels and the activities of three enzymes involved in glutathione-related scavenging will be measured.